This application proposes a transition from a P30 Core Center of Excellence in Hematology (DK056465-16) to an NIDDK-sponsored U54 Cooperative Hematology Specialized Core Center (CHSCC). This transition will facilitate collaborations, training, and resource sharing on a national level. The goal of this CHSCC is to advance research in stem cell and transplantation biology and thereby accelerate the development of new therapies. This requires resources that anticipate and meet the needs of an ever evolving research base. Our past experience has shown that new investigators can be recruited into this area of research if critical cells, technologies, and expertise can be accessed at reasonable cost. To address these needs we are proposing to provide an Administrative Core and five biomedical research cores. These include Cell Procurement and Processing, to provide large quantities of purified normal hematopoietic stem, progenitor, and stromal populations harvested from adult blood and marrow as well as cord blood and induced pluripotent stem cells (iPSC); Vector Production to provide lenti, retro, foamy and adeno-associated virus vectors for gene transduction, marking, and editing; Specialized Mouse Services including in vivo xenogeneic transplantation assays and the generation of custom transgenic models; the Canine Large Animal Model for preclinical studies including protocol development and IACUC approval; and Molecular Library Development and Screening, that provides access to CRISPR genome editing and shRNA libraries. The services provided by these cores will enable individual investigators to: 1) isolate and characterize stem/progenitor cells, 2) genetically mark, edit or otherwise alter their gene expression, 3) accurately detect and quantitate their progeny in vitro and in vivo, and 4) determine the effects of these manipulations on hematopoiesis at the molecular, cellular, and whole animal levels. The Administrative Core provides budgetary and scientific oversight of all CHSCC activities, and manages a charge back system to generate program income. Program income is used to enhance and expand Core operations as well as support the Pilot & Feasibility (P&F) and Enrichment programs designed for trainees and young investigators in the CHSCC network. Finally, the Administrative Core will work with Sage Bionetworks to create a publicly searchable data archive linking investigators to annotated data, techniques, and protocols generated through the CHSCC programs. The 30 member research base of this CHSCC receives more than 29 million/year direct costs in non-malignant Hematology-related research, 3.8 million comes directly from the NIDDK.